NCT05963217

Brief Summary

This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
1mo left

Started Jul 2023

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress98%
Jul 2023May 2026

First Submitted

Initial submission to the registry

June 27, 2023

Completed
29 days until next milestone

Study Start

First participant enrolled

July 26, 2023

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 27, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2026

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2026

Expected
Last Updated

July 2, 2025

Status Verified

June 1, 2025

Enrollment Period

2.7 years

First QC Date

June 27, 2023

Last Update Submit

June 27, 2025

Conditions

Relapsed or Refractory CD19+ B-cell LymphomaRelapsed or Refractory Chronic Lymphocytic LeukemiaRelapsed or Refractory Small Lymphocytic Lymphoma

Keywords

CD19+ B-cell LymphomaChronic Lymphocytic LeukemiaCLLSmall Lymphocytic LymphomaSLLLymphomaTBI-2001Anti-CD19 CAR Expressing T cell TherapyCD19 CAR Gene-Transduced LymphocyteAdoptive ImmunotherapyGenetically Engineered Lymphocyte TherapyRetroviral VectorNeoplasms by Histologic TypeNeoplasmsNeoplasms, ExperimentalImmune System DiseasesChimeric Antigen Receptor

Outcome Measures

Primary Outcomes (4)

  • Safety of TBI-2001

    Dose Limiting Toxicities (DLTs)

    One month

  • Safety of TBI-2001

    Adverse event (AEs)

    One year

  • Safety of TBI-2001

    Laboratory testing- RCR appearance and Clonality

    One year

  • Recommended phase 2 dose (RP2D) of TBI-2001

    RP2D to be determined during the dose escalation cohort

    One year

Secondary Outcomes (4)

  • Efficacy of TBI-2001; Overall Response Rate (ORR)

    One year

  • Efficacy of TBI-2001; Durable Response Rate (DRR)

    One year

  • Efficacy of TBI-2001; Progression free survival (PFS)

    One year

  • Efficacy of TBI-2001; Overall survival (OS)

    One year

Other Outcomes (2)

  • Persistence of TBI-2001

    One year

  • Minimal residual disease (MRD) negative rate (in CLL patients)

    One year

Study Arms (1)

Experimental: Dose Level 1 to 3

EXPERIMENTAL

0.3 to 3 x 10\^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.

Biological: TBI-2001Drug: CyclophosphamideDrug: Fludarabine

Interventions

TBI-2001BIOLOGICAL

Phase-I portion: cohort 1: 3×10\^5 cells/kg, cohort 2: 1×10\^6 cells/kg, cohort 3: 3×10\^6 cells/kg). Phase-Ib portion: The dose of Phase-Ib will be determined during the phase I portion.

Experimental: Dose Level 1 to 3
CyclophosphamideDRUG

IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.

Experimental: Dose Level 1 to 3
FludarabineDRUG

IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.

Experimental: Dose Level 1 to 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with histologically or cytologically confirmed CD19 positive B cell Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL) who have received at least 2 prior therapies.
  • Phase Ib cohort will enroll CLL/SLL patients only.
  • ECOG Performance Status 0 or 1.
  • Age ≥18 years at time of consent.
  • Life expectancy greater than 4 months.
  • For cessation of therapies prior to apheresis and lymphodepleting chemotherapy (bridging therapies), the institutional (UHN) SOPs related to Kymriah will be followed. However, an exception will be made for targeted and biological therapies that decrease circulating disease and are not expected to negatively impact successful harvest of lymphocytes by apheresis. In these cases, after discussion with and approval by the Sponsor, no washout will be required.
  • Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc)
  • Consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
  • The treating investigator should consider the patient to have disease that is incurable, and that the patient would be a reasonable candidate for future treatment with TBI-2001 within the next 3 months

You may not qualify if:

  • Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation.
  • Active or prior documented autoimmune disease within the past 2 years.
  • History of primary immunodeficiency.
  • History of organ transplant that requires use of immunosuppressive medications.
  • History hypersensitivity to components of manufacture or excipients of investigational drug.
  • Untreated central nervous system (CNS) metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
  • Other invasive malignancy within 2 years except for noninvasive malignancies
  • Current or prior use of immunosuppressive medication within 14 days before apheresis.
  • Any condition that, in the opinion of the investigator, would interfere with the evaluation of TBI-2001 or interpretation of subject safety or study results.
  • Known history of untreated active tuberculosis.
  • HIV positivity.
  • Active HTLV or syphilis infection.
  • Active hepatitis B or active hepatitis C. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted.
  • Pregnant or lactating women.
  • Received allogeneic-HSCT.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

RecurrenceLeukemia, Lymphocytic, Chronic, B-CellLymphomaNeoplasms by Histologic TypeNeoplasmsNeoplasms, ExperimentalImmune System Diseases

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersChronic Disease

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Marcus Butler, M.D.

    Princess Margaret Cancer Centre

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcus Butler, M.D.

CONTACT

416-946-4501tip@uhn.ca

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2023

First Posted

July 27, 2023

Study Start

July 26, 2023

Primary Completion

March 30, 2026

Study Completion (Estimated)

May 30, 2026

Last Updated

July 2, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)